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Abstract:

A metal buffer layer assisted guided mode resonance (GMR) biosensor is
disclosed. The GMR biosensor includes a substrate, a metal buffer layer
and a waveguide layer. The metal buffer layer is disposed on the
substrate and the waveguide layer is disposed on the metal buffer layer.
The metal buffer layer, which is disposed adjacent to the waveguide
layer, can carry out the total reflection and provide extra phase
compensation of the total reflection at the same time. Accordingly, the
propagation constant of the resonance wave would be much closer to the
sensitivity of the phase, and the resonance electric field of the GMR
biosensor would be much closer to the sensitive area. Consequently, the
sensitivity of the GMR biosensor could be improved.

Claims:

1. A guided mode resonance (GMR) biosensor, comprising: a substrate; a
metal buffer layer disposed on the substrate; and a waveguide layer
disposed on the metal buffer layer.

10. The GMR biosensor of claim 1, wherein the reflectivity of the metal
buffer layer is substantially larger than 90%.

11. The GMR biosensor of claim 2, wherein the thickness of the grating
structure is less than 1 μm.

12. The GMR biosensor of claim 3, wherein the thickness of the grating
layer is less than 1 μm.

Description:

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This Non-provisional application claims priority under 35 U.S.C.
§119(a) on Patent Application No(s). 100125528 filed in Taiwan,
Republic of China on Jul. 19, 2011, the entire contents of which are
hereby incorporated by reference.

BACKGROUND OF THE INVENTION

[0002] 1. Field of Invention

[0003] The present invention relates to a biosensor and, in particular, to
a guided mode resonance (GMR) or guided wave resonance or resonant
waveguide or photonic crystal biosensor.

[0004] 2. Related Art

[0005] Various kinds of sensors are introduced in different applications.
For example, many electronic products, vehicles and machines must be
equipped with a sensor. Some sensors usually detect the changes of
physical properties such as temperature, light and pressure. These
sensors are called physical sensors such as thermometers or pressure
gauge. Besides, some sensors are mainly applied to detect the chemical
materials, so they are also called chemical sensors such as a pH
electrode (pH meter).

[0006] However, the conventional chemical sensors can only detect the
inorganic materials rather than the organic materials. In fact, the
detection of the bio organic materials in the fields of bio-industrials,
clinical diagnosis, and environmental engineering is very important. The
conventional detecting methods for bio organic materials include the
chromogenic method, piezoelectric method, and optical spectrum analysis
method. However, these methods have the disadvantages of time consuming
and expensive equipments. Consequently, it is desired to develop a new
biosensor for detecting organic materials.

[0007] For developing a biosensor with a specific function, it is
important to consider the characteristics of the selected bio molecules,
mechanisms, signal generating/outputting modes, concentrations, operation
environment parameters. The conventional biosensors include (1)
electrochemical biosensors, (2) semiconductor transistor sensors, (3)
optical biosensors, and (4) piezoelectric quartz crystal biosensors.
Regarding to the optical biosensors, there are several popular and
critical technologies including the evanescence wave technology, surface
plasma resonance technology, and fluorescent labeling technology. The
fluorescent labeling technology includes a step of labeling the target,
so the operation time increases and the chemical reaction is more
complicated. The surface plasma resonance technology does not need the
labeling step, but it needs more detecting space for improving its
sensitivity and stability, which restricts the minimum size of the system
design with using this technology. Besides, the surface plasma resonance
technology is hard to achieve the high-throughput requirement.

[0008] The guided mode resonance (GMR) technology for biosensing does not
need the florescent labeling step, can carry out the fast sampling
process, can be manufactured in mass production, can have high capacity,
and can be manufactured by semiconductor processes so as to achieve the
minimized size, combine with other semiconductor devices, and have no
limitation in the size of the target to be detected. Therefore, it has
become one of the most popular biosensors. The GMR biosensor mainly
includes a grating element on or in a planer waveguide element. By
changing the surface effective refractive indexes, the boundary
conditions on the wave guide are changed. Similarly, the guided-wave in
the wave guide may have the optical properties with wavelength shift due
to the changed boundary conditions.

[0009] Generally, the grating element can provide the momentum in the
direction parallel to the interface to the incident light field within
the spatial frequency domain. When the wavelength of the incident light
is a resonance wavelength of the grating element, which means the
wavelength of the incident light matches the phase matching and the
coupling condition, the total internal reflection occurs in the boundary
area of the wave guide and coupled to the wave guide. In the wave guide,
the diffraction light can generate the total internal reflection at the
interface of the wave guide and the substrate, and then couple out to the
air through the upper grating interface. The light outputted through the
grating can interfere with the incident light to form the reflective
light. The zero-order light can perpendicularly pass through the wave
guide (this is the detectable transmission spectrum). The phase matching
and the coupling conditions of the resonance wavelength are very
sensitive with the environmental optical refraction index, so it is
suitable for configuring a biosensor.

[0010] Therefore, it is desired to develop a GMR biosensor with high
sensitivity.

SUMMARY OF THE INVENTION

[0011] In view of the foregoing, an objective of the present invention is
to provide a GMR biosensor with high sensitivity.

[0012] To achieve the above objective, the present invention discloses a
guided mode resonance (GMR) biosensor including a substrate, a metal
buffer layer and a waveguide layer. The metal buffer layer is disposed on
the substrate, and the waveguide layer is disposed on the metal buffer
layer.

[0013] In one embodiment, the waveguide layer includes a grating
structure.

[0014] In one embodiment, the GMR biosensor further includes a grating
layer disposed on the waveguide layer.

[0015] In one embodiment, the material of the waveguide layer includes
photonic crystals.

[0016] In one embodiment, the substrate includes a plurality of
microstructures, and the metal buffer layer and the waveguide layer are
disposed on the microstructures in order.

[0017] In one embodiment, the substrate is opaque or light-permeable.

[0018] In one embodiment, the thickness of the waveguide layer is between
50 nm and 1000 nm.

[0019] In one embodiment, the thickness of the metal buffer layer is
larger than 50 nm.

[0020] In one embodiment, the reflectivity of the metal buffer layer is
substantially larger than 90%.

[0021] In one embodiment, the thickness of the grating structure or
grating layer is less than 1 μm.

[0022] As mentioned above, the GMR biosensor of the present invention has
a metal buffer layer for carrying out the total reflection of the
signals, so that the second total reflection angle is unnecessary so as
to enhance the displacement of the resonance wavelength caused by the bio
molecules. Besides, since the metal buffer layer can provide extra phase
compensation of total reflection, the energy of the optical field may be
close to the surface of the GMR biosensor. This can further improve the
signal sensitivity.

BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The invention will become more fully understood from the detailed
description and accompanying drawings, which are given for illustration
only, and thus are not limitative of the present invention, and wherein:

[0024] FIG. 1A is a schematic diagram showing a GMR biosensor with a metal
buffer layer according to a preferred embodiment of the invention;

[0025] FIG. 1B is a schematic diagram showing another GMR biosensor with a
metal buffer layer according to the preferred embodiment of the
invention;

[0026] FIG. 1C is a schematic diagram showing another GMR biosensor with a
metal buffer layer according to the preferred embodiment of the
invention;

[0027] FIG. 1D is a schematic diagram showing another GMR biosensor with a
metal buffer layer according to the preferred embodiment of the
invention;

[0028] FIGS. 2A and 2B are schematic diagrams showing the GMR biosensor
with a metal buffer layer of the invention which is operated in the
detecting procedures;

[0029] FIG. 3A is a phase diagram of the GMR biosensor with a metal buffer
layer of the invention;

[0030] FIG. 3B is a phase diagram of a conventional GMR device; and

[0031] FIGS. 4A and 4B are schematic diagrams showing the energy intensity
of the optical fields of the GMR biosensor with a metal buffer layer of
the invention and the conventional GMR device.

DETAILED DESCRIPTION OF THE INVENTION

[0032] The present invention will be apparent from the following detailed
description, which proceeds with reference to the accompanying drawings,
wherein the same references relate to the same elements.

[0033] With reference to FIG. 1A, a guided mode resonance (GMR) biosensor
1a according to a preferred embodiment of the invention includes a
substrate 11a, a metal buffer layer 12 and a waveguide grating layer 13a.
The metal buffer layer 12 is disposed on the substrate 11a, and the
waveguide layer 13a is disposed on the metal buffer layer 12. The GMR
biosensor 1a can be used to detect the concentration or any property of
bio or chemical material with binding specificity. For example, the bio
or chemical material can be a DNA, RNA, nucleotide, peptide, protein,
enzyme, antibody, antigen, etc.

[0034] If the substrate 11a is a light-permeable substrate, such as a
glass substrate or quartz or transparent plastic substrate, the incident
light L emitted from the light source enters the GMR biosensor 1a through
the waveguide layer 13a. The signal sensor D1, D3 and D2 are disposed at
a light input side of the substrate 11a of the GMR biosensor 1a, the
opposite side, and a side parallel to the waveguide layer 13a,
respectively, for receiving the light refracted and reflected by the
waveguide layer 13a, the light passing through the waveguide layer 13a,
and the lateral leaked light. The detected result can be further
calculated and analyzed. If the substrate 11a is an opaque substrate,
such as a ceramic substrate, a printed circuit substrate, or a metal
substrate, the signal sensors D1 and D2 can still receive the light
signals. The incident light L from the light source can enter the GMR
biosensor 1a after passing through a fiber, or the light source can be a
general collimation light source. Besides, the incident light L can be a
polarized light or non-polarized light. In this embodiment, the incident
light L is a polarized light for example. In this case, a polarizer is
configured between the fiber and the GMR biosensor 1a for modulating the
incident light L into a polarized light.

[0035] The thickness of the metal buffer layer 12 is larger than 50 nm.
The material of the metal buffer layer 12 may include gold, aluminum,
silver or platinum. The reflectivity of the metal buffer layer is
substantially larger than 90%. In practice, the metal buffer layer 12 of
the embodiment is not a light-permeable layer.

[0036] In this embodiment, the waveguide layer 13a includes a grating
structure. The thickness of the waveguide layer 13a is between 50 nm and
1000 nm, and the material thereof includes photonic crystals. The grating
period is smaller than the resonance wavelength which is included in the
incident light L. Since the grating structure of the waveguide layer 13a
has a certain thickness, it can used as a waveguide layer, which has both
the grating and wave guiding functions. Of course, the waveguide layer
and the grating structure may have different aspects. For example, as
shown in FIG. 1B, the waveguide layer 13b has a planar portion 131b, and
a grating structure 132b. Alternatively, as shown in FIG. 1C, the GMR
biosensor 1c further includes a grating layer 14 disposed on the
waveguide layer 13c. The thickness of either the grating structure or the
grating layer 14 is smaller than 1 μm. In addition, the grating
structure may be formed by the microstructures of the substrate. As shown
in FIG. 1D, the substrate 11d has a plurality of microstructures having
the shape similar to the grating structure. Then, the metal buffer layer
12d and the waveguide layer 13d are formed thereon in order by sputtering
or depositing.

[0037] Referring to FIG. 1A again, the incident light L passes through the
grating and then coupled to the waveguide layer 13a, thereby forming the
resonance transmission, which called guide-mode resonance. In this
embodiment, the waveguide layer 13a may include a grating layer. After
passing through the grating layer, the incident light L may match the
couple state of the wave guide under a specific bandwidth and incident
angle. In more details, the incident light L with this specific bandwidth
can enter the waveguide layer 13a and be transmitted in resonance
therein. During performing the transmission spectrum scan of the incident
light L, the transmission of the incident light may dramatically descend
at a specific wavelength, which can indicate a detecting signal.

[0038] The light may leave the waveguide layer 13a through two interfaces.
The first interface is between the waveguide layer 13a and the buffer
solution of the sample (the GMR biosensor 1a is immersed in water or
other buffer solution), and the second interface is between the waveguide
layer 13a and the metal buffer layer 12. In the prior art, the second
interface is between the waveguide layer and the transparent substrate.
The critical angle of the second interface is larger than that of the
first interface. If the propagation angle of the resonance light inside
the waveguide layer 13a with respect to the interface is smaller than any
critical angle of the two interfaces, the guide-mode resonance as well as
the measurement of the signal fails. When the bio molecules are suspended
or dissolved in water and bind to the surface of the grating structure
through the immobilized ligand molecules, the detected resonance
wavelength signal may be shifted toward the longer wavelength. Moreover,
if the concentration of the bio molecules increases, the offset of the
resonance wavelength increases too. The present invention configures the
metal buffer layer 12 between the substrate 11a and the waveguide layer
13a so as to create the total reflection, so that it is easier to reach
the first critical angle (smaller critical angle). Therefore, the
resonance condition may approach to the high sensitivity conditions
without being interfered by the second critical angle. Moreover, the
present invention can increase the offset of the resonance wavelength and
enhance the sensitivity for detecting the bio molecules. An application
of the GMR biosensor of the present invention will be described
hereinafter. In the following example, the GMR biosensor 1c as shown in
FIG. 1C is adopted.

[0039] FIGS. 2A and 2B are schematic diagrams showing the GMR biosensor
with a metal buffer layer of the invention which is operated in the
detecting procedures.

[0040] A receptor 2 (e.g. an antibody or a single-strand DNA sequence) is
fixed to the surface of the GMR biosensor 1c. In more detailed, the
receptor 2 is bound to the surface of grating layer 14. The GMR biosensor
1c containing the fixed receptor 2 is then immersed in the liquid
specimen. The liquid specimen must contact with the grating layer 14
inside the GMR biosensor 1c. The liquid specimen contains the ligand 3
(target) for conjugating with the receptor 2. For example, the ligand 3
can be a corresponding antigen or another single-strand DNA sequence.
After a proper interaction period, the receptor 2 and the ligand 3 can
spontaneously bind with each other by attaching or bond based on their
specificity. As shown in FIG. 2B, the ligand 3 is bound with the receptor
2 fixed on the GMR biosensor 1c. Then, the GMR biosensor 1c with the
receptor 2 and ligand 3 is detected.

[0041] FIG. 3A is a phase diagram of the GMR biosensor with a metal buffer
layer of the invention, and FIG. 3B is a phase diagram of a conventional
GMR device, which does not configured with a metal buffer layer. FIG. 3B
shows two obvious sharp turning points, which indicate two critical
angles, while FIG. 3A shows only one sharp turning point in both the TE
and TM modes, which indicate one critical angle. The reflectivity of the
metal buffer layer is substantially larger than 90%. In other words, the
metal buffer layer has a planar structure with high reflectivity.

[0042] Accordingly, although there are two interfaces between the liquid
specimen, the waveguide layer and the metal buffer layer, the interface
between the waveguide layer and the metal buffer layer can generate total
reflection for the light beams from any angle. Thus, the incident light
traveling to the metal buffer layer can have total internal reflection
without considering the relation between the incident angle and the
critical angle. Compared with the conventional GMR device, the GMR
biosensor of the present invention has a metal buffer layer disposed at
one side of the waveguide layer, so the critical angle between the
conventional waveguide layer and substrate does not exist. Therefore,
only one critical angle between the liquid specimen and the waveguide
layer remains. In the GMR biosensor of the present invention, the
incident angle for causing resonance has broader limit, which is to be
larger than the critical angle of the interface between the liquid and
the waveguide layer.

[0043] FIGS. 4A and 4B are schematic diagrams showing the energy intensity
of evanescence wave of the GMR biosensor with a metal buffer layer of the
invention and the conventional GMR device. FIG. 4A shows, form top to
bottom, a glass substrate, a metal buffer layer, a waveguide layer, a
grating layer and water, and FIG. 4B shows, form top to bottom, a glass
substrate, a waveguide layer and water. In the energy distribution
figure, the brighter portion (white) represents the stronger intensity
area in the optical field. Referring to FIGS. 4A and 4B, the GMR
biosensor with a metal buffer layer of the invention can provide extra
total reflection phase compensation and can prevent the optical field
from penetrating to the substrate. Thus, the energy of the optical field
can not apply to the substrate and can be restricted around the waveguide
layer. Besides, the energy distribution is asymmetric, so the overlap
portion of the energy and the bio molecules located on the surface of the
waveguide layer is increased. Herein, the overlap portion represents the
high energy region. In the conventional GMR device, the strongest
intensity area of the optical energy is located around the waveguide
layer too, but some energy of the optical field penetrates to the
substrate. This can cause the undesired energy dissipation. It is obvious
that the energy applied to the bio molecules on the surface of the
waveguide layer in the conventional GMR device is less than that in the
GMR biosensor of the present invention. The above phenomenon can also
support the conclusion that the GMR biosensor of the present invention
can provide enhanced detection sensitivity.

[0044] Although the invention has been described with reference to
specific embodiments, this description is not meant to be construed in a
limiting sense. Various modifications of the disclosed embodiments, as
well as alternative embodiments, will be apparent to persons skilled in
the art. It is, therefore, contemplated that the appended claims will
cover all modifications that fall within the true scope of the invention.

Patent applications by Chih Cheng Chien, Taoyuan County TW

Patent applications by Wen-Yih Chen, Taoyuan County TW

Patent applications in class Including optical measuring or testing means

Patent applications in all subclasses Including optical measuring or testing means